Is BSND p.Thr6Ala (c.16A>G) pathogenic?

BSND p.Thr6Ala (c.16A>G) is classified Conflicting classifications of pathogenicity in BSND (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.2866); Rare (popmax 0.181%, eas); Associated with Bartter disease type 4A.

What condition is associated with BSND p.Thr6Ala (c.16A>G)?

BSND p.Thr6Ala (c.16A>G) is associated with Bartter disease type 4A, Bartter syndrome (ClinVar).

How common is BSND p.Thr6Ala (c.16A>G) in the general population?

BSND p.Thr6Ala (c.16A>G) is rare (popmax 0.181%, eas) (gnomAD).

What do computational predictors say about BSND p.Thr6Ala (c.16A>G)?

AlphaMissense predicts likely benign (score 0.2866) — an in-silico prediction, not a clinical call.

BSND p.Thr6Ala

c.16A>G · rs201342416 · VCV290808

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.2866 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.181%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Bartter disease type 4A

Computational evidence

Protein change
AlphaMissense	0.2866	likely benign
REVEL	0.396	indeterminate
SaProt	LLR -6.30	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.4, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 9,438 bp · p 0.065 · regional, not allelic
Overall
CADD	24.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.181% East Asian · 81/44,792 alleles

Filtering AF 0.149% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.137%

Overall 0.00601% 97/1,613,508 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.181%	553
Remaining individualsnot grpmax-eligible	0.0192%	5,209
European (non-Finnish)	0.000339%	294,966

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: BSND
Protein: p.Thr6Ala
Coding: c.16A>G
MANE Select: NM_057176
dbSNP: rs201342416
Type: single nucleotide variant
Location: chr1:54999202 (GRCh38)
Gene constraint: LOEUF 1.03 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 53.80
Residue 6: a UniProt-annotated variant site (in barts4a); the 'regulates channel membrane trafficking and ion conductance' region

Full BSND gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Bartter disease type 4A — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Bartter syndrome

Similar variants

BSND c.178-2A>C Likely pathogenic ★★ same condition
BSND c.272+1G>T Pathogenic/Likely pathogenic ★★ same condition
BSND p.Arg8Trp Pathogenic/Likely pathogenic ★★ same condition
BSND p.Gln95Ter Pathogenic/Likely pathogenic ★★ same condition
BSND p.Glu148Ter Pathogenic/Likely pathogenic ★★ same condition
BSND p.Glu4Ter Pathogenic ★★ same condition
BSND p.Glu88Ter Pathogenic/Likely pathogenic ★★ same condition
BSND p.Gly10Ser Pathogenic/Likely pathogenic ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/bsnd-p-thr6ala (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown